Abstract:
Peripheral arterial disease (PAD) is an atherosclerotic obstructive disorder of the arteries supplying nutrient-rich blood to the lower extremities. Globally, it has become the third leading cause of atherosclerotic morbidity. Among many others, ischemia-reperfusion injury (IRI) is the central manifestation of PAD where their habilitation of blood flow to a hypoxic organ proves detrimental instead of alleviating it. IRI mainly affect mitochondrial functions and initiates cell death. Though the transfer of intact healthy mitochondria into damaged organs has shown some promising results in clinical trials. However, it has left researchers with some open questions regarding the viability of mitochondria in an exogenous Ca 2+ -rich environment before being taken by the recipient cells. Our present study aimed to explore the effect of allogenic mitochondrial transplantation in a model of acute hind limb IRI, mimicking PAD. Two different mitochondrial populations (based on size) were obtained from mice liver and proceeded for their viability by performing MTT assay, mitochondrial content through protein quantification and functional integrity by MPTP opening. Acute hind limb IRI was induced by using grommets and orthodontic rubber bands (ORB) in male BALB/c albino mice and the model was then confirmed by quantifying infarct size, histological staining and the level of muscle damage characteristics enzymes; Lactate dehydrogenase (LDH) and Creatine kinase (CK). The model development was followed by in vivo mitochondrial transfer and its characterization. The data showed that relatively bigger mitochondria were more viable as compared to the smaller ones with an insignificant impact on the mitochondrial content and sensitivity to mitochondrial permeability transition pore (MPTP) opening. The in vivo experiments revealed that both grommet and ORB successfully induce IRI, by increasing infarct size in the gastrocnemius muscle with no significant difference between grommet and ORB induced IRI. Furthermore, there was a significant increase in blood LDH and CK levels. Likewise, the results from hematoxylin and eosin staining exposed raised myocyte degeneration and fatty acid accumulation in the IRI muscle. The in vivo transplantation experiments revealed successful mitigation of IRI by reducing infarct size besides reducing LDH and CK levels. Finally, the data confirms a therapeutic benefit of mitochondrial transplantation in acute hind limb IRI.
Page(s):
0-0
DOI:
DOI not available
Published:
Journal: First International Conference on Revamped Scientific Outlook of 21st Century (Abstract Book), Volume: 0, Issue: 0, Year: 2022
Keywords:
Mitochondrial transplantation
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Peripheral artery disease PAD
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Ischemiareperfusion Injury IRI
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Gastrocnemius GS muscle